Hadi Hosseini is a computational/cognitive neuroscientist investigating large-scale structural and functional brain networks in various neuropsychiatric disorders using multimodal neuroimaging, graph theoretical and multivariate pattern analyses techniques. He is also developing novel NIRS-based neurofeedback interventions for enhancing executive functions. Dr. Hosseini has been co-teaching the Neuroimaging Research Methods (Psyc250) at Stanford since 2012.
Assistant Professor (Research), Psychiatry and Behavioral Sciences - Interdisciplinary Brain Sciences
Member, Wu Tsai Neurosciences Institute
Honors & Awards
Career Development Award (K25), NIA (2016-2021)
NARSAD Young Investigator Award, Brain & Behavior Research Foundation (2016-2018)
CHRI Pilot Early Career Award, Lucile Packard Foundation for Children’s Health (2015-2016)
ICGP Junior Investigator Award, International College of Geriatric Psychoneuropharmacology (ICGP) (Aug 2015)
Best Presentation Award, APRC-IBRO School of Neuroimaging (Nov 2010)
SAND Travel award, SAND5 Conference (May 2010)
MEXT Full Scholarship for PhD Program, Tohoku University (2005-2008)
Current Research and Scholarly Interests
Our lab’s research portfolio crosses multiple disciplines including computational neuropsychiatry, cognitive neuroscience, multimodal neuroimaging and neurocognitive rehabilitation. Our computational neuropsychiatry research mainly involves investigating alterations in the organization of connectome in various neurodevelopmental and neurocognitive disorders using state of the art neuroimaging techniques (fMRI, sMRI, DWI, functional NIRS) combined with novel computational methods (graph theoretical and multivariate pattern analyses).
The ultimate goal of our research is to translate the findings from computational neuropsychiatry research toward developing personalized interventions. We have been developing personalized interventions that integrate computerized cognitive rehabilitation, real-time functional brain imaging and neurofeedback, as well as virtual reality (VR) tailored toward targeted rehabilitation of the affected brain networks in patients with neurocognitive disorders.
A Novel fNIRS Neurofeedback Intervention for Enhancement of Working Memory in Attention Deficit Hyperactivity Disorder (ADHD)
The proposed study is to test and validate a novel intervention that integrates computerized cognitive training with real-time neuromonitoring and neurofeedback to enhance working memory by probing the individualized neural systems underlying working memory. We will test the proposed intervention on children with ADHD with working memory deficits. The R61 proof-of-concept phase will assess the target engagement, effective dose and feasibility.
Stanford is currently not accepting patients for this trial. For more information, please contact Hannah Fingerhut, 650-724-2939.
The Influence of Multi-domain Cognitive Training on Large-scale Structural and Functional Brain Networks in MCI
The purpose of this study is to integrate advanced computational techniques and multimodal neuroimaging methods to examine the potential effects of long-term, multi-domain, online, computerized cognitive training on large-scale structural and functional brain networks in older adults with mild cognitive impairment (MCI).
Stanford is currently not accepting patients for this trial. For more information, please contact Hadi Hosseini, PhD, 650-724-2939.
- Methodology of Research in Behavioral Sciences
PSYC 250 (Win)
Independent Studies (4)
- Directed Study
BIOE 391 (Spr)
HUMBIO 194 (Win)
- Research in Human Biology
HUMBIO 193 (Aut, Win)
- Undergraduate Research
PSYC 199 (Aut, Win, Spr, Sum)
- Directed Study
Prior Year Courses
- Methodology of Research in Behavioral Sciences
PSYC 250 (Win)
- Methodology of Research in Behavioral Sciences
PSYC 250 (Win)
- Methodology of Research in Behavioral Sciences
PSYC 250 (Win)
- Methodology of Research in Behavioral Sciences
Doctoral Dissertation Reader (AC)
Postdoctoral Faculty Sponsor
Elveda Gozdas, Ali Rahimpour Jounghani, Amirali Vahid, Jafar Zamani
Current opinions on the present and future use of functional near-infrared spectroscopy in psychiatry.
2023; 10 (1): 013505
Functional near-infrared spectroscopy (fNIRS) is an optical imaging technique for assessing human brain activity by noninvasively measuring the fluctuation of cerebral oxygenated- and deoxygenated-hemoglobin concentrations associated with neuronal activity. Owing to its superior mobility, low cost, and good tolerance for motion, the past few decades have witnessed a rapid increase in the research and clinical use of fNIRS in a variety of psychiatric disorders. In this perspective article, we first briefly summarize the state-of-the-art concerning fNIRS research in psychiatry. In particular, we highlight the diverse applications of fNIRS in psychiatric research, the advanced development of fNIRS instruments, and novel fNIRS study designs for exploring brain activity associated with psychiatric disorders. We then discuss some of the open challenges and share our perspectives on the future of fNIRS in psychiatric research and clinical practice. We conclude that fNIRS holds promise for becoming a useful tool in clinical psychiatric settings with respect to developing closed-loop systems and improving individualized treatments and diagnostics.
View details for DOI 10.1117/1.NPh.10.1.013505
View details for PubMedID 36777700
View details for PubMedCentralID PMC9904322
Decoding the heterogeneity of Alzheimer's disease diagnosis and progression using multilayer networks.
Alzheimer's disease (AD) is a multifactorial and heterogeneous disorder, which makes early detection a challenge. Studies have attempted to combine biomarkers to improve AD detection and predict progression. However, most of the existing work reports results in parallel or compares normalized findings but does not analyze data simultaneously. We tested a multi-dimensional network framework, applied to 490 subjects (cognitively normal [CN] = 147; mild cognitive impairment [MCI] = 287; AD = 56) from ADNI, to create a single model capable of capturing the heterogeneity and progression of AD. First, we constructed subject similarity networks for structural magnetic resonance imaging, amyloid-β positron emission tomography, cerebrospinal fluid, cognition, and genetics data and then applied multilayer community detection to find groups with shared similarities across modalities. Individuals were also followed-up longitudinally, with AD subjects having, on average, 4.5 years of follow-up. Our findings show that multilayer community detection allows for accurate identification of present and future AD (≈90%) and is also able to identify cases that were misdiagnosed clinically. From all MCI participants who developed AD or reverted to CN, the multilayer model correctly identified 90.8% and 88.5% of cases respectively. We observed similar subtypes across the full sample and when examining multimodal data from subjects with no AD pathology (i.e., amyloid negative). Finally, these results were also validated using an independent testing set. In summary, the multilayer framework is successful in detecting AD and provides unique insight into the heterogeneity of the disease by identifying subtypes that share similar multidisciplinary profiles of neurological, cognitive, pathological, and genetics information.
View details for DOI 10.1038/s41380-022-01886-z
View details for PubMedID 36539525
1H-MRS neurometabolites and associations with neurite microstructures and cognitive functions in amnestic mild cognitive impairment.
2022; 36: 103159
Alzheimer's disease (AD) pathogenesis is associated with alterations in neurometabolites and cortical microstructure. However, our understanding of alterations in neurochemicals in the prefrontal cortex and their relationship with changes in cortical microstructure in AD remains unclear. Here, we studied the levels of neurometabolites in the left dorsolateral prefrontal cortex (DLPFC) in healthy older adults and patients with amnestic Mild Cognitive Impairments (aMCI) using single-voxel proton-magnetic resonance spectroscopy (1H-MRS). N-acetyl aspartate (NAA), glutamate+glutamate (Glx), Myo-inositol (mI), and gamma-aminobutyric acid (GABA) brain metabolite levels were quantified relative to total creatine (tCr=Cr+PCr). aMCI had significantly decreased NAA/tCr, Glx/tCr, NAA/mI, and increased mI/tCr levels compared with healthy controls. Further, we leveraged advanced diffusion MRI to extract neurite properties in the left DLPFC and found a significant positive correlation between NAA/tCr, related to neuronal intracellular compartment, and neurite density (ICVF, intracellular volume fraction), and a negative correlation between mI/tCr and neurite orientation (ODI) only in healthy older adults. These data suggest a potential decoupling in the relationship between neurite microstructures and NAA and mI concentrations in DLPFC in the early stage of AD. Together, our results confirm altered DLPFC neurometabolites in prodromal phase of AD and provide unique evidence regarding the imbalance in the association between neurometabolites and neurite microstructure in early stage of AD.
View details for DOI 10.1016/j.nicl.2022.103159
View details for PubMedID 36063758
Quantitative MRI Evidence for Cognitive Reserve in Healthy Elders and Prodromal Alzheimer's Disease.
Journal of Alzheimer's disease : JAD
BACKGROUND: Cognitive reserve (CR) has been postulated to contribute to the variation observed between neuropathology and clinical outcomes in Alzheimer's disease (AD).OBJECTIVE: We investigated the effect of an education-occupation derived CR proxy on biological properties of white matter tracts in patients with amnestic mild cognitive impairment (aMCI) and healthy elders (HC).METHODS: Educational attainment and occupational complexity ratings (complexity with data, people, and things) from thirty-five patients with aMCI and twenty-eight HC were used to generate composite CR scores. Quantitative magnetic resonance imaging (qMRI) and multi-shell diffusion MRI were used to extract macromolecular tissue volume (MTV) across major white matter tracts.RESULTS: We observed significant differences in the association between CR and white matter tract MTV in aMCI versus HC when age, gender, intracranial volume, and memory ability were held constant. Particularly, in aMCI, higher CR was associated with worse tract pathology (lower MTV) in the left and right dorsal cingulum, callosum forceps major, right inferior fronto-occipital fasciculus, and right superior longitudinal fasciculus (SLF) tracts. Conversely higher CR was associated with higher MTV in the right parahippocampal cingulum and left SLF in HC.CONCLUSION: Our results support compensatory CR mechanisms in aMCI and neuroprotective mechanisms in HC and suggest differential roles for CR on white matter macromolecular properties in healthy elders versus prodromal AD patients.
View details for DOI 10.3233/JAD-220197
View details for PubMedID 35964179
Cognitive impairment and associations with structural brain networks, endocrine status, and risk genotypes in newly orchiectomized testicular cancer patients.
Brain imaging and behavior
A higher incidence of cognitive impairment (CI) has previously been reported among orchiectomized testicular cancer patients (TCPs), but little is known about the underlying pathophysiology. The present study assessed CI in newly orchiectomized TCPs and explored the structural brain networks, endocrine status, and selected genotypes. Forty TCPs and 22 healthy controls (HCs) underwent neuropsychological testing and magnetic resonance imaging, and provided a blood sample. CI was defined as a z-score ≤ -2 on one neuropsychological test or ≤ -1.5 on two neuropsychological tests, and structural brain networks were investigated using graph theory. Associations of cognitive performance with brain networks, endocrine status (including testosterone levels and androgen receptor CAG repeat length), and genotypes (APOE, BDNF, COMT) were explored. Compared with HCs, TCPs performed poorer on 6 out of 15 neuropsychological tests, of which three tests remained statistically significant when adjusted for relevant between-group differences (p < 0.05). TCPs also demonstrated more CI than HCs (65% vs. 36%; p = 0.04). While global brain network analysis revealed no between-group differences, regional analysis indicated differences in node degree and betweenness centrality in several regions (p < 0.05), which was inconsistently associated with cognitive performance. In TCPs, CAG repeat length was positively correlated with delayed memory performance (r = 0.36; p = 0.02). A COMT group × genotype interaction effect was found for overall cognitive performance in TCPs, with risk carriers performing worse (p = 0.01). No effects were found for APOE, BDNF, or testosterone levels. In conclusion, our results support previous findings of a high incidence of CI in newly orchiectomized TCPs and provide novel insights into possible mechanisms.
View details for DOI 10.1007/s11682-021-00492-x
View details for PubMedID 34392471
Cognitive changes and brain connectomes, endocrine status, and risk genotypes in testicular cancer patients-A prospective controlled study.
Previous research has indicated cognitive decline (CD) among testicular cancer patients (TCPs), even in the absence of chemotherapy, but little is known about the underlying pathophysiology. The present study assessed changes in cognitive functions and structural brain connectomes in TCPs and explored the associations between cognitive changes and endocrine status and hypothesized risk genotypes.Thirty-eight newly orchiectomized TCPs and 21 healthy controls (HCs) comparable to TCPs in terms of age and years of education underwent neuropsychological testing, structural MRI, and a biological assessment at baseline and 6 months later. Cognitive change was assessed with a neuropsychological test battery and determined using a standardized regression-based approach, with substantial change defined as z-scores ≤-1.64 or ≥1.64. MRI scans and graph theory were used to evaluate changes in structural brain connectomes. The associations of cognitive changes with testosterone levels, androgen receptor gene (AR) CAG repeat length, and genotypes (APOE, COMT, and BDNF) were explored.Compared with HCs, TCPs showed higher rates of substantial decline on processing speed and visuospatial ability and higher rates of substantial improvement on verbal recall and visuospatial learning (p < 0.05; OR = 8.15-15.84). Brain network analysis indicated bilateral thalamic changes in node degree in HCs, but not in TCPs (p < 0.01). In TCPs, higher baseline testosterone levels predicted decline in verbal memory (p < 0.05). No effects were found for AR CAG repeat length, APOE, COMT, or BDNF.The present study confirms previous findings of domain-specific CD in TCPs following orchiectomy, but also points to domain-specific improvements. The results do not indicate changes in brain connectomes or endocrine status to be the main drivers of CD. Further studies evaluating the mechanisms underlying CD in TCPs, including the possible role of the dynamics of the hypothalamic-pituitary-gonadal axis, are warranted.
View details for DOI 10.1002/cam4.4165
View details for PubMedID 34390226
Neurite Imaging Reveals Widespread Alterations in Gray and White Matter Neurite Morphology in Healthy Aging and Amnestic Mild Cognitive Impairment.
Cerebral cortex (New York, N.Y. : 1991)
Aging is the major risk factor for neurodegenerative diseases and affects neurite distributions throughout the brain, yet underlying neurobiological mechanisms remain unclear. Multi-shell diffusion-weighted imaging and neurite orientation dispersion and density imaging (NODDI) now provide in vivo biophysical measurements that explain these biological processes in the cortex and white matter. In this study, neurite distributions were evaluated in the cortex and white matter in healthy older adults and patients with amnestic mild cognitive impairment (aMCI) that provides fundamental contributions regarding healthy aging and neurodegeneration. Older age was associated with reduced neurite density and neurite orientation dispersion (ODI) in widespread cortical regions. In contrast, increased ODI was only observed in the right thalamus and hippocampus with age. For the first time, we also reported a widespread age-associated decrease in neurite density along major white matter tracts correlated with decreased cortical neurite density in the tract endpoints in healthy older adults. We further examined alterations in cortical and white matter neurite microstructures in aMCI patients and found significant neurite morphology deficits in memory networks correlated with memory performance. Our findings indicate that neurite parameters provide valuable information regarding cortical and white matter microstructure and complement myeloarchitectural information in healthy aging and aMCI.
View details for DOI 10.1093/cercor/bhab180
View details for PubMedID 34313731
Functional near-infrared spectroscopy in developmental psychiatry: a review of attention deficit hyperactivity disorder
EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE
Research has linked executive function (EF) deficits to many of the behavioral symptoms of attention deficit hyperactivity disorder (ADHD). Evidence of the involvement of EF impairment in ADHD is corroborated by accumulating neuroimaging studies, specifically functional magnetic resonance imaging (fMRI) studies. However, in recent years, functional near-infrared spectroscopy (fNIRS) has become increasingly popular in ADHD research due to its portability, high ecological validity, resistance to motion artifacts, and cost-effectiveness. While numerous studies throughout the past decade have used fNIRS to examine alterations in neural correlates of EF in ADHD, a qualitative review of the reliability of these findings compared with those reported using gold-standard fMRI measurements does not yet exist. The current review aims to fill this gap in the literature by comparing the results generated from a qualitative review of fNIRS studies (children and adolescents ages 6-16 years old) to a meta-analysis of comparable fMRI studies and examining the extent to which the results of these studies align in the context of EF impairment in ADHD. The qualitative analysis of fNIRS studies of ADHD shows a consistent hypoactivity in the right prefrontal cortex in multiple EF tasks. The meta-analysis of fMRI data corroborates altered activity in this region and surrounding areas during EF tasks in ADHD compared with typically developing controls. These findings indicate that fNIRS is a promising functional brain imaging technology for examining alterations in cortical activity in ADHD. We also address the disadvantages of fNIRS, including limited spatial resolution compared with fMRI.
View details for DOI 10.1007/s00406-021-01288-2
View details for Web of Science ID 000668035700001
View details for PubMedID 34185132
The effect of body posture on resting-state functional connectivity.
INTRODUCTION: An important but under-investigated confound of functional MRI (fMRI) is body posture. Although it is well-established that body position changes cerebral blood flow, the amount of cerebrospinal fluid in the brain, intracranial pressure, and even the firing rate of certain cell types, there is currently no study that directly examines its effect on fMRI measurements. Moreover, fMRI is typically done in a supine position, which often does not correspond to how these processes are performed in everyday settings.METHODS: In this study, 20 healthy adults underwent resting-state fMRI under three body positions: supine, right lateral decubitus (RLD), and left lateral decubitus (LLD). We first investigated whether there were differences in overall organization of whole-brain connectivity between conditions using graph theory. Second, we examined whether functional connectivity of two most studied default mode network (DMN) seeds to the rest of the brain was altered as a function of body position.RESULTS: Nonparametric statistical analyses revealed that global network measures differed among conditions, with the supine and LLD showing identical results compared to the RLD. There was decreased connectivity for DMN seeds in the RLD condition compared to the supine and LLD, but there were no significant differences between the latter two conditions.DISCUSSION: Potential mechanisms underlying these alterations include gravity, changes in physiology, and body anatomy. Our results suggest that, compared to supine and LLD, the RLD position leads to changes in whole-brain and DMN connectivity. Finally, depending on the research question, combining imaging modalities that allow for more naturalistic settings can provide a better understanding of certain phenomena.
View details for DOI 10.1089/brain.2021.0013
View details for PubMedID 34114506
Androgen deprivation therapy and cognitive decline-associations with brain connectomes, endocrine status, and risk genotypes
PROSTATE CANCER AND PROSTATIC DISEASES
Evidence suggests that prostate cancer (PC) patients undergoing androgen deprivation therapy (ADT) are at risk for cognitive decline (CD), but the underlying mechanisms are less clear. In the present study, changes in cognitive performance and structural brain connectomes in PC patients undergoing ADT were assessed, and associations of cognitive changes with endocrine status and risk genotypes were explored.Thirty-seven PC patients underwent cognitive assessment, structural MRI, and provided blood samples prior to ADT and after 6 months of treatment. Twenty-seven age- and education-matched healthy controls (HCs) underwent the same assessments. CD was determined using a standardized regression-based approach and defined as z-scores ≤ -1.64. Changes in brain connectomes were evaluated using graph theory. Associations of CD with testosterone levels and genotypes (APOE, COMT, BDNF) were explored.Compared with HCs, PC patients demonstrated reduced testosterone levels (p < 0.01) and higher rates of decline for 13 out of 15 cognitive outcomes, with three outcomes related to two cognitive domains, i.e., verbal memory and visuospatial learning and memory, reaching statistical significance (p ≤ 0.01-0.04). Testosterone level changes did not predict CD. COMT Met homozygote PC patients evidenced larger reductions in visuospatial memory compared with Val carriers (p = 0.02). No between-group differences were observed in brain connectomes across time, and no effects were found of APOE and BDNF.Our results indicate that PC patients undergoing ADT may evidence CD, and that COMT Met homozygotes may be at increased risk of CD. The results did not reveal changes in brain connectomes or testosterone levels as underlying mechanisms. More research evaluating the role of ADT-related disruption of the dynamics of the hypothalamic-pituitary-gonadal axis is needed.
View details for DOI 10.1038/s41391-021-00398-1
View details for Web of Science ID 000658095400001
View details for PubMedID 34088994
Quantitative Measurement of Macromolecular Tissue Properties in White and Gray Matter in Healthy Aging and Amnestic MCI.
Healthy and pathological aging influence brain microstructure via complex processes. Discerning these processes require measurements that are sensitive to specific biological properties of brain tissue. We integrated a novel quantitative R1 measure with multi-shell diffusion weighted imaging to map age-associated changes in macromolecular tissue volume (MTV) along major white matter tracts in healthy older adults and patients with amnestic Mild Cognitive Impairment (aMCI). Reduced MTV in association tracts was associated with older age in healthy aging, was correlated with memory performance, and distinguished aMCI from controls. We also mapped changes in gray matter tissue properties using quantitative R1 measurements. We documented a widespread decrease in R1 with advancing age across cortex and decreased R1 in aMCI compared with controls in regions implicated in episodic memory. Our data are the first to characterize MTV loss along major white matter tracts in aMCI and suggest that qMRI is a sensitive measure for detecting subtle degeneration of white and gray matter tissue that cannot be detected by conventional MRI and diffusion measures.
View details for DOI 10.1016/j.neuroimage.2021.118161
View details for PubMedID 34000394
Evaluation of smartphone interactions on drivers’ brain function and vehicle control in an immersive simulated environment
View details for DOI 10.1038/s41598-021-81208-5
A low-cost, wearable, do-it-yourself functional near-infrared spectroscopy (DIY-fNIRS) headband
2021; 10: e00204
View details for DOI 10.1016/j.ohx.2021.e00204
The Effect of Baseline Performance and Age on Cognitive Training Improvements in Older Adults: A Qualitative Review
JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE
View details for DOI 10.14283/jpad.2020.55
View details for Web of Science ID 000581023500002
Focal white matter disruptions along the cingulum tract explain cognitive decline in amnestic mild cognitive impairment (aMCI).
2020; 10 (1): 10213
White matter abnormalities of the human brain are implicated in typical aging and neurodegenerative diseases. However, our understanding of how fine-grained changes in microstructural properties along white matter tracts are associated with memory and cognitive decline in normal aging and mild cognitive impairment remains elusive. We quantified tract profiles with a newer method that can reliably measure fine-grained changes in white matter properties along the tracts using advanced multi-shell diffusion magnetic resonance imaging in 25 patients with amnestic mild cognitive impairment (aMCI) and 23 matched healthy controls (HC). While the changes in tract profiles were parallel across aMCI and HC, we found a significant focal shift in the profile at specific locations along major tracts sub-serving memory in aMCI. Particularly, our findings depict white matter alterations at specific locations on the right cingulum cingulate, the right cingulum hippocampus and anterior corpus callosum (CC) in aMCI compared to HC. Notably, focal changes in white matter tract properties along the cingulum tract predicted memory and cognitive functioning in aMCI. The results suggest that white matter disruptions at specific locations of the cingulum bundle may be a hallmark for the early prediction of Alzheimer's disease and a predictor of cognitive decline in aMCI.
View details for DOI 10.1038/s41598-020-66796-y
View details for PubMedID 32576866
Glucocorticoid regulation and neuroanatomy in fragile x syndrome
Journal of Psychiatric Research
View details for DOI 10.1016/j.jpsychires.2020.12.015
Cognitive Impairment and Associations with Structural Brain Networks, Endocrine Status, and Risk Genotypes in Newly Diagnosed Prostate Cancer Patients Referred to Androgen Deprivation Therapy
View details for DOI 10.1002/cncr.33387
Accelerated intermittent theta burst stimulation in major depression induces decreases in modularity: A connectome analysis.
Network neuroscience (Cambridge, Mass.)
2019; 3 (1): 157-172
Accelerated intermittent theta burst stimulation (aiTBS) is a noninvasive neurostimulation technique that shows promise for improving clinical outcome in patients suffering from treatment-resistant depression (TRD). Although it has been suggested that aiTBS may evoke beneficial neuroplasticity effects in neuronal circuits, the effects of aiTBS on brain networks have not been investigated until now. Fifty TRD patients were enrolled in a randomized double-blind sham-controlled crossover trial involving aiTBS, applied to the left dorsolateral prefrontal cortex. Diffusion-weighted MRI data were acquired at each of three time points (T1 at baseline; T2 after the first week of real/sham aiTBS stimulation; and T3 after the second week of treatment). Graph analysis was performed on the structural connectivity to examine treatment-related changes in the organization of brain networks. Changes in depression severity were assessed using the Hamilton Depression Rating Scale (HDRS). Baseline data were compared with 60 healthy controls. We observed a significant reduction in depression symptoms over time (p < 0.001). At T1, both TRD patients and controls exhibited a small-world topology in their white matter networks. More importantly, the TRD patients demonstrated a significantly shorter normalized path length (p AUC = 0.01), and decreased assortativity (p AUC = 0.035) of the structural networks, compared with the healthy control group. Within the TRD group, graph analysis revealed a less modular network configuration between T1 and T2 in the TRD group who received real aiTBS stimulation in the first week (p < 0.013). Finally, there were no significant correlations between changes on HDRS scores and reduced modularity. Application of aiTBS in TRD is characterized by reduced modularity, already evident 4 days after treatment. These findings support the potential clinical application of such noninvasive brain stimulation in TRD.
View details for DOI 10.1162/netn_a_00060
View details for PubMedID 30793079
View details for PubMedCentralID PMC6372023
X-chromosome insufficiency alters receptive fields across the human early visual cortex.
The Journal of neuroscience : the official journal of the Society for Neuroscience
Here, we investigated processing by receptive fields, a fundamental property of neurons in the visual system, using fMRI and population receptive field (pRF) mapping in 20 human females with monosomic Turner syndrome (TS) (mean age, 10.3 ± 2.0) versus 22 age- and sex-matched controls (mean age, 10.4 ± 1.9). TS, caused by X-chromosome haploinsufficiency in females is associated with well-recognized effects on visual-spatial processing, parieto-occipital cortical anatomy, and parietal lobe function. However, it is unknown if these effects are related to altered brain structure and function in early visual areas (V1-V3) versus downstream parietal cortical regions. Results show that girls with TS have: (i) smaller volume of V1-V3, (ii) lower average pRF eccentricity in early visual areas, and (iii) sparser pRF coverage in the periphery of the visual field. Further, we examined whether the lower volume of early visual areas, defined using retinotopic mapping, in TS is due to smaller surface area or thinner cortex. Results show that girls with TS had a general reduction in surface area relative to controls in bilateral V1 and V2. Our data suggest the possibility that the smaller cortical surface area of early visual areas in girls with TS may be associated with a lower number of neurons which, in turn, leads to lesser coverage of the peripheral visual field compared to controls. These results indicate that X-chromosome haploinsufficiency associated with TS affects the functional neuroanatomy of early visual areas and suggest that investigating pRFs in TS may shed insights into their atypical visual-spatial processing.SIGNIFICANCE STATEMENTTurner syndrome is caused by the absence of one of the two X-chromosome in females. Using functional neuroimaging and population receptive field mapping, we find that chromosome dosage variation (X-monosomy) associated with Turner syndrome affects the functional neuroanatomy of the visual cortex. Specifically, girls with Turner syndrome have smaller early visual areas that provide lesser coverage of the peripheral visual field compared to healthy controls. Our observations provide compelling evidence that the X-chromosome affects not only parietal cortex, as described in previous studies, but also affects early visual areas. These findings suggest a paradigm change in understanding the effect of X-monosomy on the development of visual-spatial abilities in humans.
View details for DOI 10.1523/JNEUROSCI.2745-18.2019
View details for PubMedID 31434689
Brain circuitry, behavior, and cognition: A randomized placebo-controlled trial of donepezil in fragile X syndrome.
Journal of psychopharmacology (Oxford, England)
Fragile X syndrome, the most common inherited cause for intellectual disability, is associated with alterations in cholinergic among other neurotransmitter systems. This study investigated the effects of donepezil hydrochloride, a cholinesterase inhibitor that has potential to correct aberrant cholinergic signaling.Forty-two individuals with fragile X syndrome (mean age=19.61 years) were randomized to receive 2.5-10.0 mg of donepezil (n=20, seven females) or placebo (n=22, eight females) per day. One individual in the active group withdrew at week 7. Outcomes included the contingency naming test, the aberrant behavior checklist, and behavior and brain activation patterns during a functional magnetic resonance imaging gaze discrimination task.There were no significant differences between active and placebo groups on cognitive (contingency naming task) or behavioral (total score or subscales of the aberrant behavior checklist) outcomes. At baseline, the active and placebo groups did not differ in functional magnetic resonance imaging activation patterns during the gaze task. After 12 weeks of treatment the active group displayed reduced activation in response to the averted vs direct gaze contrast, relative to the placebo group, in the left superior frontal gyrus.Reduced functional brain activation for the active group may represent less arousal in response to direct eye gaze, relative to the placebo group. Change in functional magnetic resonance imaging activation patterns may serve as a more sensitive metric and predictor of response to treatment when compared to cognitive and behavioral assessments. Our results suggest that donepezil may have an impact on brain functioning, but longer term follow-up and concomitant behavioral intervention may be required to demonstrate improvement in cognition and behavior.
View details for DOI 10.1177/0269881119858304
View details for PubMedID 31264943
Inter-Brain Synchrony in Mother-Child Dyads During Cooperation: An fNIRS Hyperscanning Study.
Coordinated brain activity between individuals, or inter-brain synchrony, has been shown to increase during cooperation and correlate with cooperation success. However, few studies have examined parent-child inter-brain synchrony and whether it is associated with meaningful aspects of the parent-child relationship. Here, we measured inter-brain synchrony in the right prefrontal (PFC) and temporal cortices in mother-child dyads while they engaged in a cooperative and independent task. We tested whether inter-brain synchrony in mother-child dyads (1) increases during cooperation, (2) differs in mother-son versus mother-daughter dyads, and (3) is related to cooperation performance and the attachment relationship. Overall inter-brain synchrony in the right hemisphere, and the right dorsolateral and frontopolar PFC in particular, was higher during cooperation. Mother-son dyads showed less inter-brain synchrony during the independent task and a stronger increase in synchrony in response to cooperation than mother-daughter dyads. Lastly, we did not find strong evidence for links between inter-brain synchrony and child attachment. Mother-child cooperation may increase overall inter-brain synchrony, although differently for mother-son versus mother-daughter dyads. More research is needed to better understand the potential role of overall inter-brain synchrony in mother-child cooperation, and the potential link between inter-brain synchrony and attachment.
View details for PubMedID 30594570
Mind over motor mapping: Driver response to changing vehicle dynamics.
Human brain mapping
Improvements in vehicle safety require understanding of the neural systems that support the complex, dynamic task of real-world driving. We used functional near infrared spectroscopy (fNIRS) and pupilometry to quantify cortical and physiological responses during a realistic, simulated driving task in which vehicle dynamics were manipulated. Our results elucidate compensatory changes in driver behavior in response to changes in vehicle handling. We also describe associated neural and physiological responses under different levels of mental workload. The increased cortical activation we observed during the late phase of the experiment may indicate motor learning in prefrontal-parietal networks. Finally, relationships among cortical activation, steering control, and individual personality traits suggest that individual brain states and traits may be useful in predicting a driver's response to changes in vehicle dynamics. Results such as these will be useful for informing the design of automated safety systems that facilitate safe and supportive driver-car communication.
View details for PubMedID 29885097
- fNIRS measurement of cortical activation and functional connectivity during a visuospatial working memory task PLoS ONE 2018; 13(8):e0201486
Changes in Brain Structural Networks and Cognitive Functions in Testicular Cancer Patients Receiving Cisplatin-Based Chemotherapy
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
2017; 109 (12)
Cisplatin-based chemotherapy may have neurotoxic effects within the central nervous system. The aims of this study were 1) to longitudinally investigate the impact of cisplatin-based chemotherapy on whole-brain networks in testicular cancer patients undergoing treatment and 2) to explore whether possible changes are related to decline in cognitive functioning.Sixty-four newly orchiectomized TC patients underwent structural magnetic resonance imaging (T1-weighted and diffusion-weighted imaging) and cognitive testing at baseline prior to further treatment and again at a six-month follow-up. At follow-up, 22 participants had received cisplatin-based chemotherapy (CT) while 42 were in active surveillance (S). Brain structural networks were constructed for each participant, and network properties were investigated using graph theory and longitudinally compared across groups. Cognitive functioning was evaluated using standardized neuropsychological tests. All statistical tests were two-sided.Compared with the S group, the CT group demonstrated altered global and local brain network properties from baseline to follow-up as evidenced by decreases in important brain network properties such as small-worldness (P = .04), network clustering (P = .04), and local efficiency (P = .02). In the CT group, poorer overall cognitive performance was associated with decreased small-worldness (r = -0.46, P = .04) and local efficiency (r = -0.51, P = .02), and verbal fluency was associated with decreased local efficiency (r = -0.55, P = .008).Brain structural networks may be disrupted following treatment with cisplatin-based chemotherapy. Impaired brain networks may underlie poorer performance over time on both specific and nonspecific cognitive functions in patients undergoing chemotherapy. To the best of our knowledge, this is the first study to longitudinally investigate changes in structural brain networks in a cancer population, providing novel insights regarding the neurobiological mechanisms of cancer-related cognitive impairment.
View details for PubMedID 29617869
Multivariate Investigation of Brain and Behavioral Outcomes in Individuals with FMR1 Full Mutation
ELSEVIER SCIENCE INC. 2017: S299–S300
View details for DOI 10.1016/j.biopsych.2017.02.806
View details for Web of Science ID 000400348700736
A Novel fNIRS-Based Neurocognitive Intervention for Targeted Enhancement of Executive Function Network in ADHD
ELSEVIER SCIENCE INC. 2017: S258–S259
View details for DOI 10.1016/j.biopsych.2017.02.508
View details for Web of Science ID 000400348700635
Altered Brain Network Segregation in Fragile X Syndrome Revealed by Structural Connectomics
2017; 27 (3): 2249-2259
Fragile X syndrome (FXS), the most common inherited cause of intellectual disability and autism spectrum disorder, is associated with significant behavioral, social, and neurocognitive deficits. Understanding structural brain network topology in FXS provides an important link between neurobiological and behavioral/cognitive symptoms of this disorder. We investigated the connectome via whole-brain structural networks created from group-level morphological correlations. Participants included 100 individuals: 50 with FXS and 50 with typical development, age 11-23 years. Results indicated alterations in topological properties of structural brain networks in individuals with FXS. Significantly reduced small-world index indicates a shift in the balance between network segregation and integration and significantly reduced clustering coefficient suggests that reduced local segregation shifted this balance. Caudate and amygdala were less interactive in the FXS network further highlighting the importance of subcortical region alterations in the neurobiological signature of FXS. Modularity analysis indicates that FXS and typically developing groups' networks decompose into different sets of interconnected sub networks, potentially indicative of aberrant local interconnectivity in individuals with FXS. These findings advance our understanding of the effects of fragile X mental retardation protein on large-scale brain networks and could be used to develop a connectome-level biological signature for FXS.
View details for DOI 10.1093/cercor/bhw055
View details for Web of Science ID 000397636600043
Neural, physiological, and behavioral correlates of visuomotor cognitive load
Visuomotor ability is quite crucial for everyday functioning, particularly in driving and sports. While there is accumulating evidence regarding neural correlates of visuomotor transformation, less is known about the brain regions that accommodate visuomotor mapping under different cognitive demands. We concurrently measured cortical activity and pupillary response, using functional near infrared spectroscopy (fNIRS) and eye-tracking glasses, to examine the neural systems linked to pupil dilation under varying cognitive demands. Twenty-three healthy adults performed two sessions of a navigation task, in which the cognitive load was manipulated by either reversing the visuomotor mapping or increasing the speed of the moving object. We identified a region in the right superior parietal lobule that responded to both types of visuomotor load and its activity was associated with larger pupillary response and better performance in the task. Our multimodal analyses suggest that activity in this region arises from the need for increased attentional effort and alertness for visuomotor control and is an ideal candidate for objective measurement of visuomotor cognitive load. Our data extend previous findings connecting changes in pupil diameter to neural activity under varying cognitive demand and have important implications for examining brain-behavior associations in real-world tasks such as driving and sports.
View details for DOI 10.1038/s41598-017-07897-z
View details for PubMedCentralID PMC5562732
Structural Brain Connectivity and the Sit-to-Stand-to-Sit Performance in Individuals with Nonspecific Low Back Pain: A Diffusion Magnetic Resonance Imaging-Based Network Analysis.
2016; 6 (10): 795-803
Individuals with nonspecific low back pain (NSLBP) show an impaired sensorimotor control. They need significantly more time to perform five consecutive sit-to-stand-to-sit (STSTS) movements compared with healthy controls. Optimal sensorimotor control depends on the coactivation of many brain regions, which have to operate as a coordinated network to achieve correct motor output. Therefore, the examination of brain connectivity from a network perspective is crucial for understanding the factors that drive sensorimotor control. In the current study, potential alterations in structural brain networks of individuals with NSLBP and the correlation with the performance of the STSTS task were investigated. Seventeen individuals with NSLBP and 17 healthy controls were instructed to perform five consecutive STSTS movements as fast as possible. In addition, data of diffusion magnetic resonance imaging were acquired and analyzed using a graph theoretical approach. Results showed that individuals with NSLBP needed significantly more time to perform the STSTS task compared with healthy controls (p < 0.05). Both groups exhibited small-world properties in their structural networks. However, local efficiency was significantly decreased in the patients with NSLBP compared with controls (p < 0.05, false discovery rate [FDR] corrected). Moreover, global efficiency was significantly correlated with the sensorimotor task performance within the NSLBP group (r = -0.73, p = 0.002). Our data show disrupted network organization of white matter networks in patients with NSLBP, which may contribute to their persistent pain and sensorimotor disabilities.
View details for PubMedID 27421840
Altered Integration of Structural Covariance Networks in Young Children With Type 1 Diabetes.
Human brain mapping
2016; 37 (11): 4034-4046
Type 1 diabetes mellitus (T1D), one of the most frequent chronic diseases in children, is associated with glucose dysregulation that contributes to an increased risk for neurocognitive deficits. While there is a bulk of evidence regarding neurocognitive deficits in adults with T1D, little is known about how early-onset T1D affects neural networks in young children. Recent data demonstrated widespread alterations in regional gray matter and white matter associated with T1D in young children. These widespread neuroanatomical changes might impact the organization of large-scale brain networks. In the present study, we applied graph-theoretical analysis to test whether the organization of structural covariance networks in the brain for a cohort of young children with T1D (N = 141) is altered compared to healthy controls (HC; N = 69). While the networks in both groups followed a small world organization-an architecture that is simultaneously highly segregated and integrated-the T1D network showed significantly longer path length compared with HC, suggesting reduced global integration of brain networks in young children with T1D. In addition, network robustness analysis revealed that the T1D network model showed more vulnerability to neural insult compared with HC. These results suggest that early-onset T1D negatively impacts the global organization of structural covariance networks and influences the trajectory of brain development in childhood. This is the first study to examine structural covariance networks in young children with T1D. Improving glycemic control for young children with T1D might help prevent alterations in brain networks in this population. Hum Brain Mapp, 2016. © 2016 Wiley Periodicals, Inc.
View details for DOI 10.1002/hbm.23293
View details for PubMedID 27339089
Neural signature of developmental coordination disorder in the structural connectome independent of comorbid autism
2016; 19 (4): 599-612
Children with autism spectrum disorders (ASD) often exhibit motor clumsiness (Developmental Coordination Disorder, DCD), i.e. they struggle with everyday tasks that require motor coordination like dressing, self-care, and participating in sport and leisure activities. Previous studies in these neurodevelopmental disorders have demonstrated functional abnormalities and alterations of white matter microstructural integrity in specific brain regions. These findings suggest that the global organization of brain networks is affected in DCD and ASD and support the hypothesis of a 'dys-connectivity syndrome' from a network perspective. No studies have compared the structural covariance networks between ASD and DCD in order to look for the signature of DCD independent of comorbid autism. Here, we aimed to address the question of whether abnormal connectivity in DCD overlaps that seen in autism or comorbid DCD-autism. Using graph theoretical analysis, we investigated differences in global and regional topological properties of structural brain networks in 53 children: 8 ASD children with DCD (DCD+ASD), 15 ASD children without DCD (ASD), 11 with DCD only, and 19 typically developing (TD) children. We constructed separate structural correlation networks based on cortical thickness derived from Freesurfer. The children were assessed on the Movement-ABC and the Beery Test of Visual Motor Integration. Behavioral results demonstrated that the DCD group and DCD+ASD group scored on average poorer than the TD and ASD groups on various motor measures. Furthermore, although the brain networks of all groups exhibited small-world properties, the topological architecture of the networks was significantly altered in children with ASD compared with DCD and TD. ASD children showed increased normalized path length and higher values of clustering coefficient. Also, paralimbic regions exhibited nodal clustering coefficient alterations in singular disorders. These changes were disorder-specific, and included alterations in clustering coefficient in the isthmus of the right cingulate gyrus and the pars orbitalis of the right inferior frontal gyrus in ASD children, and DCD-related increases in the lateral orbitofrontal cortex. Children meeting criteria for both DCD and ASD exhibited topological changes that were more widespread from those seen in children with only DCD, i.e. children with DCD+ASD showed alterations of clustering coefficient in (para)limbic regions, primary areas, and association areas. The DCD+ASD group showed changes in clustering coefficient in the left association cortex relative to the ASD group. Finally, the DCD+ASD group shared ASD-specific abnormalities in the pars orbitalis of right inferior frontal gyrus, which was hypothesized to reflect atypical emotional-cognitive processing. Our results provide evidence that DCD and ASD are neurodevelopmental disorders with a low degree of overlap in abnormalities in connectivity. The co-occurrence of DCD+ASD was also associated with a distinct topological pattern, highlighting the unique neural signature of comorbid neurodevelopmental disorders.
View details for DOI 10.1111/desc.12424
View details for Web of Science ID 000379952100006
View details for PubMedID 27147441
Task-based neurofeedback training: A novel approach toward training executive functions
2016; 134: 153-159
Cognitive training is an emergent approach to improve cognitive functions in various neurodevelopmental and neurodegenerative diseases. However, current training programs can be relatively lengthy, making adherence potentially difficult for patients with cognitive difficulties. Previous studies suggest that providing individuals with real-time feedback about the level of brain activity (neurofeedback) can potentially help them learn to control the activation of specific brain regions. In the present study, we developed a novel task-based neurofeedback training paradigm that benefits from the effects of neurofeedback in parallel with computerized training. We focused on executive function training given its core involvement in various developmental and neurodegenerative diseases. Near-infrared spectroscopy (NIRS) was employed for providing neurofeedback by measuring changes in oxygenated hemoglobin in the prefrontal cortex. Of the twenty healthy adult participants, ten received real neurofeedback (NFB) on prefrontal activity during cognitive training, and ten were presented with sham feedback (SHAM). Compared with SHAM, the NFB group showed significantly improved executive function performance including measures of working memory after four sessions of training (100min total). The NFB group also showed significantly reduced training-related brain activity in the executive function network including right middle frontal and inferior frontal regions compared with SHAM. Our data suggest that providing neurofeedback along with cognitive training can enhance executive function after a relatively short period of training. Similar designs could potentially be used for patient populations with known neuropathology, potentially helping them to boost/recover the activity in the affected brain regions.
View details for DOI 10.1016/j.neuroimage.2016.03.035
View details for PubMedID 27015711
Sex differences in neural and behavioral signatures of cooperation revealed by fNIRS hyperscanning
Researchers from multiple fields have sought to understand how sex moderates human social behavior. While over 50 years of research has revealed differences in cooperation behavior of males and females, the underlying neural correlates of these sex differences have not been explained. A missing and fundamental element of this puzzle is an understanding of how the sex composition of an interacting dyad influences the brain and behavior during cooperation. Using fNIRS-based hyperscanning in 111 same- and mixed-sex dyads, we identified significant behavioral and neural sex-related differences in association with a computer-based cooperation task. Dyads containing at least one male demonstrated significantly higher behavioral performance than female/female dyads. Individual males and females showed significant activation in the right frontopolar and right inferior prefrontal cortices, although this activation was greater in females compared to males. Female/female dyad's exhibited significant inter-brain coherence within the right temporal cortex, while significant coherence in male/male dyads occurred in the right inferior prefrontal cortex. Significant coherence was not observed in mixed-sex dyads. Finally, for same-sex dyads only, task-related inter-brain coherence was positively correlated with cooperation task performance. Our results highlight multiple important and previously undetected influences of sex on concurrent neural and behavioral signatures of cooperation.
View details for DOI 10.1038/srep26492
View details for Web of Science ID 000377330900001
View details for PubMedID 27270754
View details for PubMedCentralID PMC4897646
Estimating individual contribution from group-based structural correlation networks.
2015; 120: 274-284
Coordinated variations in brain morphology (e.g., cortical thickness) across individuals have been widely used to infer large-scale population brain networks. These structural correlation networks (SCNs) have been shown to reflect synchronized maturational changes in connected brain regions. Further, evidence suggests that SCNs, to some extent, reflect both anatomical and functional connectivity and hence provide a complementary measure of brain connectivity in addition to diffusion weighted networks and resting-state functional networks. Although widely used to study between-group differences in network properties, SCNs are inferred only at the group-level using brain morphology data from a set of participants, thereby not providing any knowledge regarding how the observed differences in SCNs are associated with individual behavioral, cognitive and disorder states. In the present study, we introduce two novel distance-based approaches to extract information regarding individual differences from the group-level SCNs. We applied the proposed approaches to a moderately large dataset (n=100) consisting of individuals with fragile X syndrome (FXS; n=50) and age-matched typically developing individuals (TD; n=50). We tested the stability of proposed approaches using permutation analysis. Lastly, to test the efficacy of our method, individual contributions extracted from the group-level SCNs were examined for associations with intelligence scores and genetic data. The extracted individual contributions were stable and were significantly related to both genetic and intelligence estimates, in both typically developing individuals and participants with FXS. We anticipate that the approaches developed in this work could be used as a putative biomarker for altered connectivity in individuals with neurodevelopmental disorders.
View details for DOI 10.1016/j.neuroimage.2015.07.006
View details for PubMedID 26162553
Dynamics of the connectome in Huntington's disease: A longitudinal diffusion MRI study
2015; 9: 32-43
To longitudinally investigate the connectome in different stages of Huntington's disease (HD) by applying graph theoretical analysis to diffusion MRI data.We constructed weighted structural networks and calculated their topological properties. Twenty-two premanifest (preHD), 10 early manifest HD and 24 healthy controls completed baseline and 2 year follow-up scans. We stratified the preHD group based on their predicted years to disease onset into a far (preHD-A) and near (preHD-B) to disease onset group. We collected clinical and behavioural measures per assessment time point.We found a significant reduction over time in nodal betweenness centrality both in the early manifest HD and preHD-B groups as compared to the preHD-A and control groups, suggesting a decrease of importance of specific nodes to overall network organization in these groups (FDR adjusted ps < 0.05). Additionally, we found a significant longitudinal decrease of the clustering coefficient in preHD when compared to healthy controls (FDR adjusted p < 0.05), which can be interpreted as a reduced capacity for internodal information processing at the local level. Furthermore, we demonstrated dynamic changes to hub-status loss and gain both in preHD and early manifest HD. Finally, we found significant cross-sectional as well as longitudinal relationships between graph metrics and clinical and neurocognitive measures.This study demonstrates divergent longitudinal changes to the connectome in (pre) HD compared to healthy controls. This provides novel insights into structural correlates associated with clinical and cognitive functions in HD and possible compensatory mechanisms at play in preHD.
View details for DOI 10.1016/j.nicl.2015.07.003
View details for Web of Science ID 000373188400005
View details for PubMedID 26288754
View details for PubMedCentralID PMC4536305
Neural correlates of cognitive intervention in persons at risk of developing Alzheimer's disease
FRONTIERS IN AGING NEUROSCIENCE
Cognitive training is an emergent approach that has begun to receive increased attention in recent years as a non-pharmacological, cost-effective intervention for Alzheimer's disease (AD). There has been increasing behavioral evidence regarding training-related improvement in cognitive performance in early stages of AD. Although these studies provide important insight about the efficacy of cognitive training, neuroimaging studies are crucial to pinpoint changes in brain structure and function associated with training and to examine their overlap with pathology in AD. In this study, we reviewed the existing neuroimaging studies on cognitive training in persons at risk of developing AD to provide an overview of the overlap between neural networks rehabilitated by the current training methods and those affected in AD. The data suggest a consistent training-related increase in brain activity in medial temporal, prefrontal, and posterior default mode networks, as well as increase in gray matter structure in frontoparietal and entorhinal regions. This pattern differs from the observed pattern in healthy older adults that shows a combination of increased and decreased activity in response to training. Detailed investigation of the data suggests that training in persons at risk of developing AD mainly improves compensatory mechanisms and partly restores the affected functions. While current neuroimaging studies are quite helpful in identifying the mechanisms underlying cognitive training, the data calls for future multi-modal neuroimaging studies with focus on multi-domain cognitive training, network level connectivity, and individual differences in response to training.
View details for DOI 10.3389/fnagi.2014.00231
View details for Web of Science ID 000340934900001
View details for PubMedID 25206335
View details for PubMedCentralID PMC4143724
Altered resting state functional connectivity in young survivors of acute lymphoblastic leukemia.
Pediatric blood & cancer
2014; 61 (7): 1295-1299
Chemotherapy treatment for pediatric acute lymphoblastic leukemia (ALL) has been associated with long-term cognitive impairments in some patients. However, the neurobiologic mechanisms underlying these impairments, particularly in young survivors, are not well understood. This study aimed to examine intrinsic functional brain connectivity in pediatric ALL and its relationship with cognitive status.We obtained resting state functional magnetic resonance imaging (rsfMRI) and cognitive testing data from 15 ALL survivors age 8-15 years and 14 matched healthy children. The ALL group had a history of intrathecal chemotherapy treatment but were off-therapy for at least 6 months at the time of enrollment. We used seed-based analyses to compare intrinsic functional brain network connectivity between the groups. We also explored correlations between connectivity and cognitive performance, demographic, medical, and treatment variables.We demonstrated significantly reduced connectivity between bilateral hippocampus, left inferior occipital, left lingual gyrus, bilateral calcarine sulcus, and right amygdala in the ALL group compared to controls. The ALL group also showed regions of functional hyperconnectivity including right lingual gyrus, precuneus, bilateral superior occipital lobe, and right inferior occipital lobe. Functional hypoconnectivity was associated with reduced cognitive function as well as younger age at diagnosis in the ALL group.This is the first study to demonstrate that intrinsic functional brain connectivity is disrupted in pediatric ALL following chemotherapy treatment. These results help explain cognitive dysfunction even when objective test performance is seemingly normal. Children diagnosed at a younger age may show increased vulnerability to altered functional brain connectivity.
View details for DOI 10.1002/pbc.25022
View details for PubMedID 24619953
View details for PubMedCentralID PMC4028071
Multivariate pattern analysis of FMRI in breast cancer survivors and healthy women.
Journal of the International Neuropsychological Society
2014; 20 (4): 391-401
Advances in breast cancer (BC) treatments have resulted in significantly improved survival rates. However, BC chemotherapy is often associated with several side effects including cognitive dysfunction. We applied multivariate pattern analysis (MVPA) to functional magnetic resonance imaging (fMRI) to find a brain connectivity pattern that accurately and automatically distinguishes chemotherapy-treated (C+) from non-chemotherapy treated (C-) BC females and healthy female controls (HC). Twenty-seven C+, 29 C-, and 30 HC underwent fMRI during an executive-prefrontal task (Go/Nogo). The pattern of functional connectivity associated with this task discriminated with significant accuracy between C+ and HC groups (72%, p = .006) and between C+ and C- groups (71%, p = .012). However, the accuracy of discrimination between C- and HC was not significant (51%, p = .46). Compared with HC, behavioral performance of the C+ and C- groups during the task was intact. However, the C+ group demonstrated altered functional connectivity in the right frontoparietal and left supplementary motor area networks compared to HC, and in the right middle frontal and left superior frontal gyri networks, compared to C-. Our results provide further evidence that executive function performance may be preserved in some chemotherapy-treated BC survivors through recruitment of additional neural connections. (JINS, 2013, 19, 1-11).
View details for DOI 10.1017/S1355617713001173
View details for PubMedID 24135221
View details for PubMedCentralID PMC3969386
Anomalous gray matter structural networks in major depressive disorder.
2013; 74 (10): 777-785
BACKGROUND: Major depressive disorder (MDD) is characterized by abnormalities in structure, function, and connectivity in several brain regions. Few studies have examined how these regions are organized in the brain or investigated network-level structural aberrations that might be associated with depression. METHODS: We used graph analysis to examine the gray matter structural networks of individuals diagnosed with MDD (n = 93) and a demographically similar healthy comparison group (n = 151) with no history of psychopathology. The efficiency of structural networks for processing information was determined by quantifying local interconnectivity (clustering) and global integration (path length). We also compared the groups on the contributions of high-degree nodes (i.e., hubs) and regional network measures, including degree (number of connections in a node) and betweenness (fraction of short path connections in a node). RESULTS: Depressed participants had significantly decreased clustering in their brain networks across a range of network densities. Compared with control subjects, depressed participants had fewer hubs primarily in medial frontal and medial temporal areas, had higher degree in the left supramarginal gyrus and right gyrus rectus, and had higher betweenness in the right amygdala and left medial orbitofrontal gyrus. CONCLUSIONS: Networks of depressed individuals are characterized by a less efficient organization involving decreased regional connectivity compared with control subjects. Regional connections in the amygdala and medial prefrontal cortex may play a role in maintaining or adapting to depressive pathology. This is the first report of anomalous large-scale gray matter structural networks in MDD and provides new insights concerning the neurobiological mechanisms associated with this disorder.
View details for DOI 10.1016/j.biopsych.2013.03.005
View details for PubMedID 23601854
Comparing connectivity pattern and small-world organization between structural correlation and resting-state networks in healthy adults.
2013; 78: 402-414
In recent years, coordinated variations in brain morphology (e.g. volume, thickness, surface area) have been employed as a measure of structural association between brain regions to infer large-scale structural correlation networks (SCNs). However, it remains unclear how morphometric correlations relate to functional connectivity between brain regions. Resting-state networks (RSNs), derived from coordinated variations in neural activity at rest, have been shown to reflect connectivity between functionally related regions as well as, to some extent, anatomical connectivity between brain regions. Therefore, it is intriguing to investigate similarities between SCN and RSN to help identify how morphometric correlations relate to connections defined by resting-state connectivity. We investigated the similarities in connectivity patterns and small-world organization between SCN, derived from correlations of regional gray matter volume across individuals, and RSN in 36 healthy individuals. The results showed a significant similarity between SCN and RSN (60% for positive connections and 40% for negative connections) that might be explained by shared experience-related functional connectivity underlying both SCN and RSN. Conversely, the small-world parameters of the networks were significantly different, suggesting that SCN topological parameters cannot be regarded as a substitute for topological organization in resting-state networks. While our data suggest that using structural correlation networks can be useful in understanding alterations in structural associations in various brain disorders, it should be noted that a portion of the observed alterations might be explained by factors other than those reflecting resting-state connectivity.
View details for DOI 10.1016/j.neuroimage.2013.04.032
View details for PubMedID 23603348
Cognitive Training for Improving Executive Function in Chemotherapy-Treated Breast Cancer Survivors
CLINICAL BREAST CANCER
2013; 13 (4): 299-306
BACKGROUND: A majority of breast cancer (BC) survivors, particularly those treated with chemotherapy, experience long-term cognitive deficits that significantly reduce quality of life. Among the cognitive domains most commonly affected include executive functions (EF), such as working memory, cognitive flexibility, multitasking, planning, and attention. Previous studies in other populations have shown that cognitive training, a behavioral method for treating cognitive deficits, can result in significant improvements in a number of cognitive skills, including EF. MATERIALS AND METHODS: In this study, we conducted a randomized controlled trial to investigate the feasibility and preliminary effectiveness of a novel, online EF training program in long-term BC survivors. A total of 41 BC survivors (21 active, 20 wait list) completed the 48 session training program over 12 weeks. The participants were, on average, 6 years after therapy. Results: Cognitive training led to significant improvements in cognitive flexibility, verbal fluency and processing speed, with marginally significant downstream improvements in verbal memory as assessed via standardized measures. Self-ratings of EF skills, including planning, organizing, and task monitoring, also were improved in the active group compared with the wait list group. CONCLUSIONS: Our findings suggest that EF skills may be improved even in long-term survivors by using a computerized, home-based intervention program. These improvements may potentially include subjective EF skills, which suggest a transfer of the training program to real-world behaviors.
View details for DOI 10.1016/j.clbc.2013.02.004
View details for Web of Science ID 000321239600011
View details for PubMedID 23647804
Default mode network connectivity distinguishes chemotherapy-treated breast cancer survivors from controls
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2013; 110 (28): 11600-11605
Breast cancer (BC) chemotherapy is associated with cognitive changes including persistent deficits in some individuals. We tested the accuracy of default mode network (DMN) resting state functional connectivity patterns in discriminating chemotherapy treated (C+) from non-chemotherapy (C-) treated BC survivors and healthy controls (HC). We also examined the relationship between DMN connectivity patterns and cognitive function. Multivariate pattern analysis was used to classify 30 C+, 27 C-, and 24 HC, which showed significant accuracy for discriminating C+ from C- (91.23%, P < 0.0001) and C+ from HC (90.74%, P < 0.0001). The C- group did not differ significantly from HC (47.06%, P = 0.60). Lower subjective memory function was correlated (P < 0.002) with greater hyperplane distance (distance from the linear decision function that optimally separates the groups). Disrupted DMN connectivity may help explain long-term cognitive difficulties following BC chemotherapy.
View details for DOI 10.1073/pnas.1214551110
View details for Web of Science ID 000321827000085
View details for PubMedID 23798392
View details for PubMedCentralID PMC3710809
Influence of Choice of Null Network on Small-World Parameters of Structural Correlation Networks
2013; 8 (6)
In recent years, coordinated variations in brain morphology (e.g., volume, thickness) have been employed as a measure of structural association between brain regions to infer large-scale structural correlation networks. Recent evidence suggests that brain networks constructed in this manner are inherently more clustered than random networks of the same size and degree. Thus, null networks constructed by randomizing topology are not a good choice for benchmarking small-world parameters of these networks. In the present report, we investigated the influence of choice of null networks on small-world parameters of gray matter correlation networks in healthy individuals and survivors of acute lymphoblastic leukemia. Three types of null networks were studied: 1) networks constructed by topology randomization (TOP), 2) networks matched to the distributional properties of the observed covariance matrix (HQS), and 3) networks generated from correlation of randomized input data (COR). The results revealed that the choice of null network not only influences the estimated small-world parameters, it also influences the results of between-group differences in small-world parameters. In addition, at higher network densities, the choice of null network influences the direction of group differences in network measures. Our data suggest that the choice of null network is quite crucial for interpretation of group differences in small-world parameters of structural correlation networks. We argue that none of the available null models is perfect for estimation of small-world parameters for correlation networks and the relative strengths and weaknesses of the selected model should be carefully considered with respect to obtained network measures.
View details for DOI 10.1371/journal.pone.0067354
View details for Web of Science ID 000321148400063
View details for PubMedID 23840672
View details for PubMedCentralID PMC3696118
Topological properties of large-scale structural brain networks in children with familial risk for reading difficulties
2013; 71: 260-274
Developmental dyslexia is a neurobiological deficit characterized by persistent difficulty in learning to read in children and adults who otherwise possess normal intelligence. Functional and structural connectivity data suggest that developmental dyslexia could be a disconnection syndrome. However, whether abnormalities in connectivity exist in beginning readers at-risk for reading difficulties is unknown. Using graph-theoretical analysis, we investigated differences in global and regional topological properties of structural brain networks in 42 beginning readers with (FH+) and without (FH-) familial risk for reading difficulties. We constructed separate structural correlation networks based on measures of surface area and cortical thickness. Results revealed changes in topological properties in brain regions known to be abnormal in dyslexia (left supramarginal gyrus, left inferior frontal gyrus) in the FH+ group mainly in the network constructed from measures of cortical surface area. We also found alterations in topological properties in regions that are not often advertised as dyslexia but nonetheless play important role in reading (left posterior cingulate, hippocampus, and left precentral gyrus). To our knowledge, this is the first report of altered topological properties of structural correlation networks in children at risk for reading difficulty, and motivates future studies that examine the mechanisms underlying how these brain networks may mediate the influences of family history on reading outcome.
View details for DOI 10.1016/j.neuroimage.2013.01.013
View details for Web of Science ID 000316154400026
View details for PubMedID 23333415
View details for PubMedCentralID PMC3655726
Compensatory Effort Parallels Midbrain Deactivation during Mental Fatigue: An fMRI Study
2013; 8 (2)
Fatigue reflects the functioning of our physiological negative feedback system, which prevents us from overworking. When fatigued, however, we often try to suppress this system in an effort to compensate for the resulting deterioration in performance. Previous studies have suggested that the effect of fatigue on neurovascular demand may be influenced by this compensatory effort. The primary goal of the present study was to isolate the effect of compensatory effort on neurovascular demand. Healthy male volunteers participated in a series of visual and auditory divided attention tasks that steadily increased fatigue levels for 2 hours. Functional magnetic resonance imaging scans were performed during the first and last quarter of the study (Pre and Post sessions, respectively). Tasks with low and high attentional load (Low and High conditions, respectively) were administrated in alternating blocks. We assumed that compensatory effort would be greater under the High-attentional-load condition compared with the Low-load condition. The difference was assessed during the two sessions. The effect of compensatory effort on neurovascular demand was evaluated by examining the interaction between load (High vs. Low) and time (Pre vs. Post). Significant fatigue-induced deactivation (i.e., Pre>Post) was observed in the frontal, temporal, occipital, and parietal cortices, in the cerebellum, and in the midbrain in both the High and Low conditions. The interaction was significantly greater in the High than in the Low condition in the midbrain. Neither significant fatigue-induced activation (i.e., Pre
[PreE- PostE]) may reflect suppression of the negative feedback system that normally triggers recuperative rest to maintain homeostasis.
View details for DOI 10.1371/journal.pone.0056606
View details for Web of Science ID 000315602700086
View details for PubMedID 23457592
View details for PubMedCentralID PMC3573002
Altered resting state functional brain network topology in chemotherapy-treated breast cancer survivors
NEUROBIOLOGY OF DISEASE
2012; 48 (3): 329-338
Many women with breast cancer, especially those treated with chemotherapy, experience cognitive decline due in part to neurotoxic brain injury. Recent neuroimaging studies suggest widespread brain structural abnormalities pointing to disruption of large-scale brain networks. We applied resting state functional magnetic resonance imaging and graph theoretical analysis to examine the connectome in breast cancer survivors treated with chemotherapy relative to healthy comparison women. Compared to healthy females, the breast cancer group displayed altered global brain network organization characterized by significantly decreased global clustering as well as disrupted regional network characteristics in frontal, striatal and temporal areas. Breast cancer survivors also showed significantly increased self-report of executive function and memory difficulties compared to healthy females. These results suggest that topological organization of both global and regional brain network properties may be disrupted following breast cancer and chemotherapy. This pattern of altered network organization is believed to result in reduced efficiency of parallel information transfer. This is the first report of alterations in large-scale functional brain networks in this population and contributes novel information regarding the neurobiologic mechanisms underlying breast cancer-related cognitive impairment.
View details for DOI 10.1016/j.nbd.2012.07.009
View details for Web of Science ID 000309694000007
View details for PubMedID 22820143
View details for PubMedCentralID PMC3461109
GAT: A Graph-Theoretical Analysis Toolbox for Analyzing Between-Group Differences in Large-Scale Structural and Functional Brain Networks
2012; 7 (7)
In recent years, graph theoretical analyses of neuroimaging data have increased our understanding of the organization of large-scale structural and functional brain networks. However, tools for pipeline application of graph theory for analyzing topology of brain networks is still lacking. In this report, we describe the development of a graph-analysis toolbox (GAT) that facilitates analysis and comparison of structural and functional network brain networks. GAT provides a graphical user interface (GUI) that facilitates construction and analysis of brain networks, comparison of regional and global topological properties between networks, analysis of network hub and modules, and analysis of resilience of the networks to random failure and targeted attacks. Area under a curve (AUC) and functional data analyses (FDA), in conjunction with permutation testing, is employed for testing the differences in network topologies; analyses that are less sensitive to the thresholding process. We demonstrated the capabilities of GAT by investigating the differences in the organization of regional gray-matter correlation networks in survivors of acute lymphoblastic leukemia (ALL) and healthy matched Controls (CON). The results revealed an alteration in small-world characteristics of the brain networks in the ALL survivors; an observation that confirm our hypothesis suggesting widespread neurobiological injury in ALL survivors. Along with demonstration of the capabilities of the GAT, this is the first report of altered large-scale structural brain networks in ALL survivors.
View details for DOI 10.1371/journal.pone.0040709
View details for Web of Science ID 000306406700047
View details for PubMedID 22808240
View details for PubMedCentralID PMC3396592
Altered small-world properties of gray matter networks in breast cancer
Breast cancer survivors, particularly those treated with chemotherapy, are at significantly increased risk for long-term cognitive and neurobiologic impairments. These deficits tend to involve skills that are subserved by distributed brain networks. Additionally, neuroimaging studies have shown a diffuse pattern of brain structure changes in chemotherapy-treated breast cancer survivors that might impact large-scale brain networks.We therefore applied graph theoretical analysis to compare the gray matter structural networks of female breast cancer survivors with a history of chemotherapy treatment and healthy age and education matched female controls.Results revealed reduced clustering coefficient and small-world index in the brain network of the breast cancer patients across a range of network densities. In addition, the network of the breast cancer group had less highly interactive nodes and reduced degree/centrality in the frontotemporal regions compared to controls, which may help explain the common impairments of memory and executive functioning among these patients.These results suggest that breast cancer and chemotherapy may decrease regional connectivity as well as global network organization and integration, reducing efficiency of the network. To our knowledge, this is the first report of altered large-scale brain networks associated with breast cancer and chemotherapy.
View details for DOI 10.1186/1471-2377-12-28
View details for Web of Science ID 000306755500001
View details for PubMedID 22632066
View details for PubMedCentralID PMC3404945
Altered Small-World Properties of Gray Matter Networks in Major Depression
67th Annual Meeting of the Society-of-Biological-Psychiatry
ELSEVIER SCIENCE INC. 2012: 106S–106S
View details for Web of Science ID 000302466000336
Decoding what one likes or dislikes from single-trial fNIRS measurements
2011; 22 (6): 269-273
Recent functional neuroimaging studies have shown the possibility of decoding human mental states from their brain activity using noninvasive neuroimaging techniques. In this study, we applied multivariate pattern classification, in conjunction with a short interval of functional near-infrared spectroscopy measurements of the anterior frontal cortex, to decode whether a human likes or dislikes a presented visual object; an ability that is quite beneficial for a number of clinical and technological applications. A variety of objects comprising sceneries, cars, foods, and animals were used as the stimuli. The results showed the possibility of predicting subjective preference from a short interval of functional near-infrared spectroscopy measurements of the anterior frontal regions. In addition, the pattern localization results showed the neuroscientific validity of the constructed classifier.
View details for DOI 10.1097/WNR.0b013e3283451f8f
View details for Web of Science ID 000288987800003
View details for PubMedID 21372746
- Changes in neural correlates of outcome feedback processing during implicit learning Open Neuroscience Journal 2011; 5: 24-30
Aging and decision making under uncertainty: Behavioral and neural evidence for the preservation of decision making in the absence of learning in old age
2010; 52 (4): 1514-1520
Decision making under uncertainty is an essential component of everyday life. Recent psychological studies suggest that older adults, despite age-related neurological decline, can make advantageous decisions when information about the contingencies of the outcomes is available. In this study, a two-choice prediction paradigm has been used, in conjunction with functional magnetic resonance imaging (fMRI), to investigate the effects of normal aging on neural substrates underlying uncertain decision making in the absence of learning that have not been addressed in previous neuroimaging studies. Neuroimaging results showed that both the healthy older and young adults recruited a network of brain regions comprising the right dorsolateral prefrontal cortex, bilateral inferior parietal lobule, medial frontal cortex, and right lateral orbitofrontal cortex during the prediction task. As was hypothesized, the performance of older adults in the prediction task was not impaired compared to young adults. Although no significant age-related increases in brain activity have been found, we observed an age-related decrease in activity in the right inferior parietal lobule. We speculate that the observed age-related decrease in parietal activity could be explained by age-related differences in decision making behavior revealed by questionnaire results and maximizing scores. Together, this study demonstrates behavioral and neural evidence for the preservation of decision making in older adults when information about the contingencies of the outcome is available.
View details for DOI 10.1016/j.neuroimage.2010.05.008
View details for Web of Science ID 000280695200039
View details for PubMedID 20472072
Neural bases of goal-directed implicit learning
2009; 48 (1): 303-310
Several neuropsychological and neuroimaging studies have been performed to clarify the neural bases of implicit learning, but the question of which brain regions are involved in different forms of implicit learning, including goal-directed learning and habit learning, has not yet been resolved. The present study sought to clarify the mechanisms of goal-directed implicit learning by examining the sugar production factory (SPF) task in conjunction with functional magnetic resonance imaging (fMRI). Several brain regions were identified that contribute to learning in the SPF task. Significant learning-related decreases in brain activity were found in the right inferior parietal lobule (IPL), left superior frontal gyrus, right medial frontal gyrus, cerebellar vermis, and left inferior frontal gyrus, while significant learning-related increases in activity were observed in the right inferior frontal gyrus, left precenteral gyrus and, left precuneus. Among these regions, we speculate that the IPL and medial frontal gyrus may specifically be involved in the early stage of goal-directed implicit learning. We also attempted to investigate the role of the striatum, which has a significant role in habit learning, during learning of the SPF task. The results of ROI analysis showed no learning-related change in the activity of the striatum. Although some of the observed learning-related activations in this study have also been previously reported in neuroimaging studies of habit learning, the possibility that specific brain regions involved in goal-direct implicit learning cannot be excluded.
View details for DOI 10.1016/j.neuroimage.2009.06.007
View details for Web of Science ID 000269321100033
View details for PubMedID 19524051
- Analyzing control display movement compatibility: A neuroimaging study LNCS 2009; 5639: 187-196
- Combining static/dynamic fault trees and event trees using Bayesian networks LNCS 2007; 4680: 93-99
- Event tree analysis with dependent branches using Bayesian networks Proceedings of PSAM'08 2006
- Dynamic Bayesian networks: Modeling problem Proceedings of PSAM'08 2006